Dequalinium-based functional nanosomes show increased mitochondria targeting and anticancer effect.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Mitochondrial Biology

Background:

• Mitochondria are crucial therapeutic targets for various human disorders.
• Current drug delivery systems lack efficient mitochondrial targeting capabilities.
• Novel carriers are needed for effective mitochondrial disease therapies.

Purpose of the Study:

• To develop and evaluate nanosomes (DQA80s) for dual mitochondrial targeting and anticancer therapy.
• To assess DQA80s' efficacy in cellular uptake, endolysosomal escape, and mitochondrial targeting.
• To investigate the anticancer mechanisms of DQA80s in vitro.

Main Methods:

• Synthesis of DQA80s (Dequalinium/DOTAP/DOPE nanosomes).
• Cytotoxicity assays and cellular uptake studies comparing DQA80s and DQAsomes.
• Confocal microscopy, flow cytometry, and TEM imaging for mitochondrial targeting verification.
• Analysis of apoptosis induction via ROS production, mitochondrial membrane potential, and caspase-3 activation.

Main Results:

• DQA80s exhibited higher cytotoxicity and cellular uptake than DQAsomes.
• Efficient endolysosomal escape and direct mitochondrial targeting of DQA80s were confirmed.
• DQA80s induced apoptosis through ROS generation, MAPK pathways, mitochondrial dysfunction, and caspase-3 activation.

Conclusions:

• DQA80s demonstrate significant potential as dual-action therapeutics for mitochondrial diseases.
• These nanosomes effectively target mitochondria and possess anticancer properties.
• DQA80s represent a promising drug delivery platform for mitochondria-related disorders.